Details of the Drug

General Information of Drug (ID: DMSCDY9)

• Drug Name: Mannitol
• Synonyms: Diosmol; Hexahydroxyhexane; Invenex; Isotol; MTL; Manita; Mannazucker; Mannidex; Mannigen; Mannistol; Mannit; Mannite; Osmitrol; Osmofundin; Osmosal; Resectisol; Cordycepic acid; Cpd without stereochemical designation; Manna sugar; Mannitol [USAN]; Marine Crystal; Resectisol In Plastic Container; M0044; Mannidex 16700; Mannogem 2080; D-mannite; D-mannitol; DL-Mannitol; MANNITOL 25%; Maniton-S; Mannitol (USP); Mannitol (VAN); Mannitol 10%; Mannitol 10% In Plastic Container; Mannitol 15%; Mannitol 15% In Plastic Container; Mannitol 20%; Mannitol 20% In Plastic Container; Mannitol 5%; Mannitol 5% In Plastic Container; OSMITROL 10% IN WATER IN PLASTIC CONTAINER; OSMITROL 15% IN WATER IN PLASTIC CONTAINER; OSMITROL 20% IN WATER IN PLASTIC CONTAINER; OSMITROL 5% IN WATER IN PLASTIC CONTAINER; Osmitrol (TN); Osmitrol 10% In Water; Osmitrol 15% In Water; Osmitrol 20% In Water; Osmitrol 5% In Water; SDM No. 35; SORBITOL-MANNITOL IN PLASTIC CONTAINER; Sorbitol-Mannitol; D-Mannitol (JP15); MANNITOL 10% W/ DEXTROSE 5% IN DISTILLED WATER; D-(-)-Mannitol; ED1D1E61-FEFB-430A-AFDC-D1F4A957FC3D; MANNITOL 15% DEXTROSE 5% IN SODIUM CHLORIDE 0.45%; MANNITOL 5% DEXTROSE 5% IN SODIUM CHLORIDE 0.12%; (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol; (L)-Mannitol

Indication

Disease Entry	ICD 11	Status	REF
Bronchiectasis	CA24	Approved	[1]
Cerebral edema	8D60.1	Approved	[2]
Cystic fibrosis	CA25	Approved	[2]
Edema	MG29	Approved	[2]
Ocular hypertension	9C61.01	Approved	[2]
Pseudotumor cerebri	N.A.	Approved	[2]
Renal failure	GB60-GB6Z	Approved	[1]

• Therapeutic Class: Sweetening Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 182.17
  Logarithm of the Partition Coefficient (xlogp); -3.1
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 6
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 73.15 mgh/L [3]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 13.71 mg/L [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.5 h [3]
  Clearance: The renal clearance of drug is 4.4 L/h [3]
  Elimination: Following oral inhalation of 635 mg of mannitol in healthy volunteers, 55% of the total dose was recovered unchanged in the urine; following oral or intravenous administration of 500 mg, the corresponding values were 54 and 87%, respectively [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4.7 hours [3]
  Metabolism: The drug is metabolized via the liver []
  Vd: The volume of distribution (Vd) of drug is 34.3 L [3]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Apoptosis	Not Available	PTK2	OT3Q1JDY	[4]
Apoptosis	Not Available	AKT1	OT8H2YY7	[4]

• Chemical Identifiers:
  Formula: C6H14O6
  IUPAC Name: (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol
  Canonical SMILES: C([C@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O)O
  InChI: InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5-,6-/m1/s1
  InChIKey: FBPFZTCFMRRESA-KVTDHHQDSA-N
• Cross-matching ID:
  PubChem CID: 6251
  ChEBI ID: CHEBI:16899
  CAS Number: 69-65-8
  DrugBank ID: DB00742
  TTD ID: D0P7EK
  VARIDT ID: DR00859
  INTEDE ID: DR2323
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aspergillus Mannitol 2-dehydrogenase (Asperg M2DH)	TTTX5M8	M2DH_ASPFU	Activator	[5]
Aspergillus Mannitol-1-phosphate 5-dehydrogenase (Asperg mpdA)	TTV0PE2	MTLD_ASPFU	Activator	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[6]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Gene/Protein Processing	[7]
Focal adhesion kinase 1 (PTK2)	OT3Q1JDY	FAK1_HUMAN	Drug Response	[4]
H(+)/Cl(-) exchange transporter 3 (CLCN3)	OTEEXNMU	CLCN3_HUMAN	Drug Response	[8]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Gene/Protein Processing	[9]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Gene/Protein Processing	[10]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Drug Response	[4]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Gene/Protein Processing	[10]
Tumor protein D52 (TPD52)	OTPKSK43	TPD52_HUMAN	Gene/Protein Processing	[10]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Mannitol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Framycetin	DMF8DNE	Major	Increased risk of nephrotoxicity by the combination of Mannitol and Framycetin.	Alcoholic liver disease [DB94]	[11]
Kanamycin	DM2DMPO	Major	Increased risk of nephrotoxicity by the combination of Mannitol and Kanamycin.	Bacterial infection [1A00-1C4Z]	[11]
Streptomycin	DME1LQN	Major	Increased risk of nephrotoxicity by the combination of Mannitol and Streptomycin.	Bacterial infection [1A00-1C4Z]	[11]
Gentamicin	DMKINJO	Major	Increased risk of nephrotoxicity by the combination of Mannitol and Gentamicin.	Bacterial infection [1A00-1C4Z]	[11]
Netilmicin	DMRD1QK	Major	Increased risk of nephrotoxicity by the combination of Mannitol and Netilmicin.	Bacterial infection [1A00-1C4Z]	[11]
Levomilnacipran	DMV26S8	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Levomilnacipran.	Chronic pain [MG30]	[12]
Sertraline	DM0FB1J	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Sertraline.	Depression [6A70-6A7Z]	[12]
Vilazodone	DM4LECQ	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Vilazodone.	Depression [6A70-6A7Z]	[12]
Vortioxetine	DM6F1PU	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Vortioxetine.	Depression [6A70-6A7Z]	[12]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Desvenlafaxine.	Depression [6A70-6A7Z]	[12]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[13]
Digitoxin	DMWVIGP	Moderate	Increased risk of hypomagnesemia by the combination of Mannitol and Digitoxin.	Heart failure [BD10-BD1Z]	[14]
Captopril	DM458UM	Moderate	Additive hypotensive effects by the combination of Mannitol and Captopril.	Hypertension [BA00-BA04]	[15]
Perindopril	DMOPZDT	Moderate	Additive hypotensive effects by the combination of Mannitol and Perindopril.	Hypertension [BA00-BA04]	[15]
Quinapril	DMR8H31	Moderate	Additive hypotensive effects by the combination of Mannitol and Quinapril.	Hypertension [BA00-BA04]	[15]
Sibutramine	DMFJTDI	Moderate	Increased risk of hyponatremia by the combination of Mannitol and Sibutramine.	Obesity [5B80-5B81]	[12]
Plazomicin	DMKMBES	Major	Increased risk of nephrotoxicity by the combination of Mannitol and Plazomicin.	Urinary tract infection [GC08]	[11]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 016080.
• [2] Mannitol FDA Label
• [3] FDA Approved Drug Products: BRONCHITOL (mannitol) oral inhalation powder
• [4] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [5] Polyol-specific long-chain dehydrogenases/reductases of mannitol metabolism in Aspergillus fumigatus: biochemical characterization and pH studies o... Chem Biol Interact. 2009 Mar 16;178(1-3):274-82.
• [6] Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis. J Cell Physiol. 2000 Jan;182(1):24-32. doi: 10.1002/(SICI)1097-4652(200001)182:1<24::AID-JCP3>3.0.CO;2-6.
• [7] Insulin-like growth factor I prevents mannitol-induced degradation of focal adhesion kinase and Akt. J Biol Chem. 2002 Jul 26;277(30):27393-400. doi: 10.1074/jbc.M201963200. Epub 2002 May 14.
• [8] Differential expression and roles of volume-activated chloride channels in control of growth of normal and cancerous nasopharyngeal epithelial cells. Biochem Pharmacol. 2012 Feb 1;83(3):324-34. doi: 10.1016/j.bcp.2011.11.007. Epub 2011 Nov 18.
• [9] [Plasma levels of atrial natriuretic factor (ANF) in the stroke patients after glycerol and mannitol infusion]. Zhonghua Yi Xue Za Zhi (Taipei). 1990 Aug;46(2):86-90.
• [10] Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity. Toxicol Sci. 2011 Dec;124(2):278-90. doi: 10.1093/toxsci/kfr225. Epub 2011 Aug 27.
• [11] Athlin L, Domellof L, Holm S "Gentamicin treatment in severe surgical infections: serum levels, interactions, toxicity and efficacy." Acta Chir Scand 147 (1981): 225-30. [PMID: 7034430]
• [12] Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
• [13] Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc, Marlborough, MA.
• [14] Brown DD, Dormois JC, Abraham GN, et al "Effect of furosemide on the renal excretion of digoxin." Clin Pharmacol Ther 20 (1976): 395-400. [PMID: 975715]
• [15] Burnakis TG, Mioduch HJ "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med 144 (1984): 2371-2. [PMID: 6391404]